Background: The purpose of this study was to assess bone densitometry parameters in patients with classical and hypermobile Ehlers-Danlos syndrome (EDS) and to determine whether the hypermobile subtype increases the risk of low bone mass, which is particularly important in this patient group, since the genetic mutation responsible for this subtype is still unknown. Material and Methods: In order to conduct this study, we collaborated with the EDS society in Poland. A total of 30 females of reproductive age who were included in the study were divided into two groups: Group 1-those with classical EDS (n = 9) and Group 2-those with hypermobile EDS (n = 21). Routine laboratory test results, bone turnover markers, and densitometry parameters were evaluated and compared. Results: The study groups showed no differences in terms of densitometry parameters or markers of calcium-phosphate metabolism. A multivariate logistic analysis demonstrated no increase in the risk of low bone mass (defined as a Z-score lower than -2) in patients with hypermobile EDS (OR 0.067 [95% Cl 0.0-20.927]; p = 0.356). Conclusions: The hypermobile subtype of EDS does not increase the risk of low bone mass; there were no significant differences between patients with hypermobile EDS and those with classical EDS in terms of either densitometry parameters or markers of calcium-phosphate metabolism. Although patients with hypermobile EDS are not at a higher risk of developing low bone mineral density, they should be regularly monitored for any calcium and phosphate metabolism abnormalities.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: The enhanced application of imaging techniques is resulting in the diagnosis of more patients with asymptomatic metastatic esophagogastric cancer (mEGC). We conducted a Delphi study to gather insights from European experts on the optimal timing for initiating palliative systemic therapy for these patients. METHODS: An online survey featured 14 scenarios where physicians chose their preferred timing for initiating systemic therapy: immediate(<3 weeks) or deferred. The standard scenario was a 65-year-old male, WHO/ECOG 0 with asymptomatic mEGC, 2 metastases in each lung, HER2 -, PDL1-CPS 2. In every subsequent case, one characteristic was modified. To investigate the fortitude of the physicians' preference for an immediate start, scenarios also included a patient who was motivated to start but preferred to defer if the physician deemed it judicious. Consensus was defined as ≥ 75 % agreement; scenarios without consensus were re-evaluated in Delphi round 2. RESULTS: Thirty-nine physicians participated in the first round, and 33 in the second round. Consensus to start treatment immediately was reached in 12 (86 %) scenarios. When patients preferred to defer, the consensus was to still advise to start palliative systemic treatment immediately in half (n = 7) of the scenarios. Only 2 scenarios (pre-existent WHO/ECOG 2 or 78 years old) reached the consensus that treatment could be deferred. CONCLUSIONS: In asymptomatic mEGC, immediate start of treatment is preferred by European experts. Consensus was established that treatment can be deferred for patients who prefer deferral and either have a pre-existent WHO/ECOG performance status of 2 or are of advanced age.

• MeSH
• asymptomatické nemoci terapie   MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• časové faktory MeSH
• delfská metoda * MeSH
• konsensus MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jícnu * patologie   farmakoterapie   MeSH
• nádory žaludku * farmakoterapie   patologie   MeSH
• paliativní péče * metody   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47-0.99) and PFS (HR: 0.67, 95%CI 0.49-0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.

• MeSH
• humanizované monoklonální protilátky terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• inhibitory kontrolních bodů * terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   mortalita   patologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• monoklonální protilátky MeSH
• nádory močového měchýře farmakoterapie   patologie   mortalita   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza * MeSH
• urologické nádory farmakoterapie   mortalita   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.

• MeSH
• dospělí MeSH
• fetální krev * chemie   MeSH
• inhibitory Janus kinas terapeutické užití   MeSH
• komplikace těhotenství farmakoterapie   MeSH
• lidé MeSH
• mateřské mléko * chemie   MeSH
• novorozenec MeSH
• piperidiny * terapeutické užití   MeSH
• pyrimidiny * terapeutické užití   MeSH
• těhotenství MeSH
• ulcerózní kolitida farmakoterapie   krev   MeSH
• výsledek těhotenství * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Mechanically ventilated patients have disturbed sleep. AIM OF THE STUDY: To explore whether there is a relationship between successful or unsuccessful weaning of patients and their sleep quality and circadian rhythm. MATERIALS AND METHODS: A scoping review. The search process involved four online databases: CINAHL, MEDLINE, ProQuest, and ScienceDirect. Original studies published between January 2020 and October 2022 were included in the review. RESULTS: Six studies met the inclusion criteria. These studies showed that patients with difficult weaning were more likely to have atypical sleep, shorter REM sleep, and reduced melatonin metabolite excretion. Muscle weakness was an independent factor associated with prolonged weaning from mechanical ventilation and was significantly more frequent in patients with atypical sleep. Heterogeneous patient samples and the methodology of the studies hamper a clear interpretation of the results. CONCLUSIONS: A relationship was found between abnormal sleep patterns, reduced melatonin metabolite (6-sulfa-toxymelatonin) excretion, and unsuccessful weaning. However, the causality is not clear from the existing research.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18-55 years, FEV1 > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV1 ≥ 20% (PC20) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV1 from post-diluent baseline during 0-3 h and 3-8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV1 and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV1 % predicted did not differ between MR and DR at baseline, but DR had lower median PC20M (0.84 (range 0.07-7.51) vs. MR (2.15 (0.53-11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV1), the maximal % change from baseline following M and HDM challenge were correlated. PC20M was inversely correlated with the % change in FEV1 and the % change in Xrs5 during the LAR (r= -0.443; p = 0.0018 and r= -0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

Cryptosporidium mortiferum, a parasite transmitted by squirrels, is beginning to spread in Europe. C. mortiferum was detected in a symptomatic human. A 44-year-old man from the Czech Republic suffered from gastroenteritis characterized by abdominal pain, nausea, and loose stools. Molecular analyses confirmed the XIVaA20G2T1 subtype in the patient's stool. At the same time, the same subtype of C. mortiferum was detected in three red squirrels and two ground squirrels in the area where the patient lived. The intensity of the infection was significantly higher in the red squirrels that died, while the ground squirrels showed no symptoms. The results of the study indicate that red squirrels and ground squirrels are the reservoirs for the infection.

• MeSH
• Cryptosporidium * izolace a purifikace   genetika   klasifikace   MeSH
• dospělí MeSH
• feces * parazitologie   MeSH
• fylogeneze MeSH
• gastroenteritida parazitologie   veterinární   MeSH
• kryptosporidióza * parazitologie   epidemiologie   MeSH
• lidé MeSH
• Sciuridae * parazitologie   MeSH
• zdroje nemoci parazitologie   MeSH
• zoonózy * parazitologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH

Artificial intelligence (AI) has significantly impacted numerous industries, including health care, dentistry, and specifically prosthodontics. This review focuses on AI's role in prosthodontics, detailing its use in diagnosis, design, and manufacturing. AI-driven systems analyze intraoral scans, improve prosthetic planning, and aid in robotic procedures. Emerging technologies, such as generative AI for prosthetic design and AI-driven material innovation, are discussed alongside the ethical and regulatory challenges facing broader adoption. The review highlights AI's potential to transform prosthodontic workflows, facilitating more accurate, efficient, and personalized care, while also pointing to future developments such as real-time monitoring and enhanced collaboration platforms.

• MeSH
• design s pomocí počítače MeSH
• lidé MeSH
• stomatologická protetika * metody   MeSH
• umělá inteligence * MeSH
• zubní protéza - design metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cannabidiol (CBD) is one of the principal constituents of Cannabis Sativa with no psychoactive properties. CBD is a promising neuroprotective compound bearing anti-inflammatory and antioxidant properties. However, considering its low solubility, CBD delivery to the retina represents an unresolved issue. The first aim was to investigate the potential neuroprotective effects of CBD in an in vivo model of retinal excitotoxicity induced by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Rats underwent intravitreal co-injection of AMPA (42 nmol) and CBD (10-4 M). The neuroprotective effect of CBD was investigated with histology and immunohistochemical evaluation of inflammatory and oxidative stress biomarkers. CBD reversed the AMPA-induced total retinal, inner nuclear layer and inner plexiform layer shrinkage and loss of amacrine cells. Moreover, CBD decreased the AMPA induced number of cleaved caspase-3, Iba-1 and nitrotyrosine (NT) positive cells. Based on this evidence, we developed a nanotechnological formulation of CBD to overcome critical issues related to its eye delivery. Particularly, nanostructured lipid carriers (NLC) loaded with CBD were prepared, optimized and characterized. Due to the optimal physicochemical characteristics, CBD-NLC3 has been selected and the in vitro release profile has been investigated. Additionally, CBD-NLC3 was topically administered to rats, and retinal CBD levels were determined. CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (Cmax = 98 ± 25.9 ng/mg; Tmax = 60 min), showing a high translational value. In conclusion, these findings showed a good PD/PK profile of CBD warranting further pre-clinical and clinical evaluation of the new formulation for the treatment of retinal degenerative diseases.

• MeSH
• kanabidiol * farmakokinetika   farmakologie   aplikace a dávkování   MeSH
• kaspasa 3 metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová toxicita   MeSH
• mikrofilamentové proteiny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• neuroprotektivní látky * farmakokinetika   farmakologie   aplikace a dávkování   MeSH
• nosiče léků chemie   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• proteiny vázající vápník MeSH
• retina * účinky léků   metabolismus   patologie   MeSH
• tyrosin analogy a deriváty   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH